Amphiregulin (AR) was observed by immunohistochemistry in biopsies of human venous stasis ulcers.Because tissue macrophages involved in wound repair derive from circulating monocytes, this research project intended to examine monocyte-derived growth factors and cytokines in the wound healing process. Using differential RT-PCR to semi-quantitate AR mRNA, freshly isolated human monocytes expressed AR mRNA following treatment with either lipopolysaccaride or "platelet releasate" . While waiting for the cloning by Dr. Tarnuzer of an internal RNA template for a quantitative competitive RT-PCR assay for 5 ligands and 4 receptors of the EGF Family, the questions we addressed were adequate answered in March by Mograbi, et al (Eur. Cytokine Netw., 8: 73-81, 1997) Activated monocyte lines, as well as peripheral blood monocytes, were reported to undergo a dramatic increase in AR, HRG, and HB-EGF mRNA , without a concomitant increase in EGFR, erbB-2 or erbB-4 transcripts. This indicates a paracrine role for monocyte growth factors. Thus, work on this project in our lab has been stopped. Ligands (growth factors, cytokines, etc.) and their receptors represent a major aspect of new product development within the biotechnology industry. Several members of the EGF supergene family (for example EGF, TGF-a, HB-EGF, ERG-R, erbB-2) are currently products at the pre-IND or IND stage. Research in the Cellular Pathology Section of LCB, DCB, OTRR, CBER on Amphiregulin's participation in wound healing will contribute directly to its development as a pharmaceutical product, and will enhance the capacity of CBER to accomplish scientific-based regulation of wound healing products of the EGF family, as well as PDGF-BB, Activated Platelet Supernatatant, Topical, and TGF-b, all of which are under active development as topical wound healing biologics.